Stories

Making Heart Surgery Obsolete

Dr. Mark Majesky’s research could revolutionize treatments for
everything from heart disease to muscular dystrophy.

The 2,000-square-foot zebrafish facility at Seattle Children’s Research Institute is the biggest in Seattle and has space for more than 3,000 tanks.
Drs. Mark Majesky and Lisa Maves study zebrafish because the minnow-sized fish can regenerate damaged or defective tissue – and their transparent
embryos allow researchers to monitor their development.

Think of Dr. Mark Majesky as a scientific detective, called
in to solve one of biology’s most enduring mysteries.

Majesky is unraveling how stem cells transform into
the vast array of specialized cells that build the body’s
cardiovascular system. By understanding how everything
(heart cells, brain cells and muscle cells) first forms,
Majesky is moving a giant step closer to therapies that
repair childhood disorders without surgery.

“We’re developing tools that could revolutionize how
we treat heart defects, muscular dystrophy and many
other serious conditions,” Majesky says.

Stem cells to repair hearts

Zebrafish embryos are
exciting to study because
they are transparent and
develop quickly.

The core of Majesky’s work is an initiative to develop stem
cell treatments for heart problems. One in 100 children is
born with a heart defect, and standard treatment can include
open-heart surgery and sometimes even a heart transplant.
Majesky wants to make these therapies obsolete by
“reprogramming” a person’s own cells so they help the heart
heal itself.

One of his projects aims to fix septal defects, which occur
when a child is born with a hole in one of the heart’s walls. Majesky’s goal is to insert new genes into heart cells,
instructing them to build tissue that closes the hole. His
first step is to understand how stem cells make heart
tissue, and why they don’t always do their job right.

“When you’re trying to regenerate an organ or part of
an organ, sometimes the best clues come from how it was
put together in the first place,” he says.

Majesky is particularly interested in knowing how blood
vessels form. Such knowledge has implications that extend
far beyond the heart. For instance, he is collaborating on a
project that could lead to new cancer treatments.

“When you’re trying to regenerate an organ or part of
an organ, sometimes the best clues come from how it was
put together in the first place.”

Dr. Mark Majesky

The project builds on the work of European researchers,
who found that the drug propanolol rapidly eliminates blood
vessels in hemangiomas – tumors that appear on infants’
heads and necks. He is working with a team in hopes that
understanding how the drug works will eventually lead to
understanding how tumors grow blood vessels.

“If we can figure out how hemangiomas get their blood
supply, we could potentially interrupt that process and stop
tumors from growing or spreading,” Majesky says.

Building a dream team

Majesky’s research is taking major steps forward thanks
to Loie Robinson, a Seattle Children’s donor who was so
inspired by Majesky’s work that she contributed $1.75 million
to his research.

“Mark’s work has amazing potential to transform
children’s lives, and I jumped at the opportunity to help
speed up his progress,” Robinson says.

Stem cell biology is so complicated that understanding
it requires experts with different specialties. Robinson’s
gifts are helping Majesky build a “dream team” that includes
researchers like Dr. Lisa Maves, who investigates how
different kinds of muscle cells – including the ones that
drive the heart – develop. Maves left the Fred Hutchinson
Cancer Research Center to work alongside Majesky. She
hopes to make muscle cells invulnerable to muscular
dystrophy, a condition that weakens people’s muscles
until they stop working.

“There’s a tremendous need to cure this disease,” Maves
says. “And Seattle Children’s has a unique group of clinical
doctors and researchers who are working together toward
that goal.”

Robinson’s donation also helped Majesky’s lab buy key
equipment, including a $350,000 confocal microscope that
can take time-lapse photos of stem cells from the moment
they start developing. This helps researchers understand
how stem cells function and how they can be manipulated
to repair birth defects.

The Robinson–Majesky partnership highlights how private
donations accelerate research that could ultimately save
children’s lives around the world.

“Private donations provide critical seed money for
innovative new projects,” Majesky says. “And that lets us
generate the results we need to apply for larger grants.”

“You can never be 100% sure, but I’m very confident that
discoveries by Mark and our other biologists will translate
into bedside treatments that improve children’s lives,”
Lewin says. “And I think that’s going to happen in relatively
short order.”

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Seattle Children’s provides healthcare without regard to race, color, religion (creed), sex, gender identity or expression, sexual orientation, national origin (ancestry) or disability. Financial assistance for medically necessary services is based on family income and hospital resources and is provided to children under age 21 whose primary residence is in Washington, Alaska, Montana or Idaho.